CAJ | 학술논문

目的检验吉非替尼在体条件下对正常肺的影响,及与放射联合应用时是否加重肺损伤.方法 160只小鼠分为5个组对照组(C)、吉非替尼组(G)、照射组(R)、照射后吉非替尼组(R+G)、吉非替尼后照射组(G+R).全肺照射12 Gy.吉非替尼200 mg/kg体重,周一至五与照射相隔24h给予.照射后第1、2、4、6个月观察肺泡灌洗液巨嗜细胞计数、羟脯氨酸含量、肺纤维化评分及血浆转化生长因子(TGF-β1)含量.单因素方差分析各组差异.结果第4、6个月R、R+G和G+R组巨嗜细胞计数明显高于C组(q=2.95 ～8.61,P均＜0.05),但3个组间相似(q=0.37 ～3.49,P均＞0.05).G组1、4、6个月显著低于R、R+G、G+R组(q=3.37 ～6.25,P均＜0.05).G、R、R+G、G+R组羟脯氨酸含量和肺纤维化评分均高于C组(q =3.14～4.76,P均＜0.05),但4个组间相似(q=0.70 ～4.19,P均＞0.05).R、R+G、G+R组各时间点、G组第1、2个月TGF-β1高于C组(q=3.76～8.09,P均＜0.05).结论吉非替尼单药可致BalB/C小鼠肺纤维化,与照射合用并未显著增加各自的肺损伤.吉非替尼单药所致纤维化其机制可能与照射所致的不同,需进一步实验证实.
목적 검험길비체니재체조건하대정상폐적영향,급여방사연합응용시시부가중폐손상.방법 160지소서분위5개조대조조(C)、길비체니조(G)、조사조(R)、조사후길비체니조(R+G)、길비체니후조사조(G+R).전폐조사12 Gy.길비체니200 mg/kg체중,주일지오여조사상격24h급여.조사후제1、2、4、6개월관찰폐포관세액거기세포계수、간포안산함량、폐섬유화평분급혈장전화생장인자(TGF-β1)함량.단인소방차분석각조차이.결과 제4、6개월R、R+G화G+R조거기세포계수명현고우C조(q=2.95 ～8.61,P균＜0.05),단3개조간상사(q=0.37 ～3.49,P균＞0.05).G조1、4、6개월현저저우R、R+G、G+R조(q=3.37 ～6.25,P균＜0.05).G、R、R+G、G+R조간포안산함량화폐섬유화평분균고우C조(q =3.14～4.76,P균＜0.05),단4개조간상사(q=0.70 ～4.19,P균＞0.05).R、R+G、G+R조각시간점、G조제1、2개월TGF-β1고우C조(q=3.76～8.09,P균＜0.05).결론 길비체니단약가치BalB/C소서폐섬유화,여조사합용병미현저증가각자적폐손상.길비체니단약소치섬유화기궤제가능여조사소치적불동,수진일보실험증실.
Objective To evaluate the effect on lung injury of gefitinib or/and radiation.Methods Totally 160 mice were divided into five groups:control (C) ;gefitinib (G) ;radiation (R) ;gefitinib followed by irradiation ( G + R) ;and R + G.12 Gy irradiation was delivered.Geiitinib fed by 200 mg/kg once daily for 3 weeks.Mice were sacrificed on 1,2,4 or 6 months after radiation.Macrophage count of lung lavage fluid and hydroxyproline assessed,lung fibrosis scored.and plasma TGF-β1 concentration assayed.One-way ANOVA was used to test the significance. Results The lung lavage macrophage cell number were significantly higher in group R,R + G and G + R than group C ( q =2.95 - 8.61,all P ＜ 0.05 ) on 4 and 6months,yet no significant difference between the three groups ( q =0.37 -3.49,all P ＜ 0.05 ) ; The macrophage was significantly lower in month 1,4 and 6 in group G than R,R + G and G + R ( q =3.37- 6.25,all P ＜ 0.05 ).The hydroxyproline content and the fibrosis score of G,R,R + G and G + R were significantly higher than C ( q =3.14 - 4.76,all P ＜ 0.05 ),but no significant difference between the four groups ( q =0.70 - 4.19,all P ＞ 0.05 ).The TGF-β1 concentration of R,G + R,R + G at all time points and TGF-β1 concentration of G at 1 st and 2nd months were significantly higher than C ( q =3.76 -8.09,all P ＜ 0.05).Conclusions Gefitinib could cause lung fibrosis in vivo in BalB/C mouse.The combination of gefitinib and radiation did not significantly exacerbate lung injury caused byeither alone.The mechanism of lung fibrosis caused by gefitinib might be different from that by radiation which needs further research.